Understanding the Role of Systemic Inflammation in Alzheimer’s Disease
Abstract
Human and animal studies suggest that inflammation occurring outside the central nervous system (systemic inflammation) may play a key role in promoting neurodegeneration, Alzheimer's disease pathology, and cognitive decline in older adults. Systemic inflammation, which is marked by increased blood levels of circulating proinflammatory cytokines and chemokines, may occur as a result of events such as infection, chronic disease, and physical and psychological stress, but may also occur outside the context of these conditions as a result of subclinical processes such as cellular senescence. Proinflammatory cytokines within the body can promote a proinflammatory environment in the central nervous system by crossing the blood-brain barrier, signaling through endothelial cells or circumventricular organs, and by stimulating the vagus nerve, which signals the detection of inflammatory proteins via direct afferent connections to the brain stem. Through each of these routes, systemic inflammation is believed to induce reactive, proinflammatory microglia and astrocytic phenotypes which can promote tau hyperphosphorylation, β-amyloid oligomerization, complement activation, and the breakdown of neurotransmitters into potentially harmful bioactive metabolites. Together, these molecular changes are believed initiate or exacerbate neurodegenerative processes that can eventually lead to cognitive decline and dementia in vulnerable older adults.
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Systemic inflammation is currently beginning to be considered a contributor to AD development.
“In addition, not limited to neuroinflammatory response, systemic inflammation is currently beginning to be considered a contributor to AD development of AD [106, 107].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [107]
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Recent insights into viral infections as a trigger and accelerator in alzheimer's disease
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- Authors
- Walker, K. A., Ficek, B. N., & Westbrook, R.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Walker, Keenan A.
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-06-26
- Volume
- 10
- Issue
- 8
- Pages
- 3340-3342
- ISSN
- 1948-7193 (ISSN-L)
- OpenAlex
- W2954317829
- Cited by
- 259
- References
- 5
- Citations by year
- 2026: 26 · 2025: 37 · 2024: 59 · 2023: 43 · 2022: 29 · 2021: 47 · 2020: 15 · 2019: 3
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG027668)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- systemic inflammation, Alzheimer's disease, neuroinflammation, inflammatory cytokines, chemokines, blood-brain barrier, vagus nerve, microglial activation, astrocytes, tau hyperphosphorylation, amyloid oligomerization, complement activation, cellular senescence, cognitive decline, dementia, older adults
- MeSH terms
- Alzheimer Disease, Animals, Humans, Inflammation, Neuroimmunomodulation
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